An intensive effort in LIR was aimed at delineating the immunopathogenic mechanisms of HIV infection as well as the nature of the immune response to HIV. We developed promonocytic and T cell clones which were latently or chronically infected with HIV expression. We demonstrated that normal cytokines such as lipopolysaccharide-induced monocyte supernatants were capable of inducing HIV expression in these cell lines. In addition, recombinant TNF-alpha and TNF-beta induced HIV expression in these lines. We further demonstrated at the molecular level that these cytokines induced HIV expression by a transactivating mechanism on the LTR of HIV. We demonstrated that IFN-alpha, but not AZT was capable of blocking the induction of HIV from these chronically infected cell lines by interferting with the late stage of virus budding, while not interfering with the synthesis of viral proteins. We demonstrated that HIV infects human monocytes in vitro and that the infection is a low-level chronic infection without significant without significant cytopathic effect. In addition, we cultured HIV from monocytes of HIV infected individuals. We demonstrated for the first time that human bone marrow progenitor cells could be infected with HIV. The infected cells were myelomonocytic cells; HIV was produced in large quantities intracellularly in these cells with little virus budding and minimal cytopathic effect. These studies indicate that the bone marrow may serve as an important reservoir of HIV infection and may also explain certain of the hematologic abnormalities seen in some HIV infected individuals. We developed for the first time HIV-specific, MHC-restricted cytotoxic T cell clones from HIV infected individuals. These studies will have important implications in delineating the fine specificity of the cytotoxic T cell response to HIV. Finally, by employing a novel assay system, we demonstrated the presence of antibodies from HIV- infected individuals which block the binding of the envelope protein of HIV to its CD4 cellular receptor.